Straightforward molecular dynamics trajectories have been computed to explore the diffusion of carbon monoxide through myoglobin. The classical equations of motion were integrated for 2 ns and the resulting pathways analyzed. Two types of runs were examined. Type i: Myoglobin and a ligand embedded in a periodic box with 9996 water molecules; the water molecules are rigid but the bonds of the protein are flexible. Type ii: Myoglobin with a solvation shell (153 water molecules) in which all bond lengths are fixed. In trajectories of type i, the diffusing ligand visits a significant part of the protein matrix and was not constrained to the proximity of the heme pocket before escaping. The maximum time of the trajectories was 2 ns. It was shorter if the ligand escaped earlier. Two ligands (from a total of 88) escape to the solvent from nonclassical gates (non-E-helix gates). In trajectories of type ii, the overall fluctuations of the protein are smaller and the ligand explores significantly smaller internal space. The escape rate from type ii trajectories (11 of 400) is comparable to type i and is not dramatically different from experiment (I of 100). Interestingly, the two simulations with comparable rates sampled different pathways. In trajectories of type ii, we observe escapes from the classical gate (His 64) and from the Xe4 cavity. Further studies (that are underway) are required to define the escape pathways and the overall rate.